Abstract
Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 577-585 |
| Number of pages | 9 |
| Journal | Journal of Gastroenterology |
| Volume | 46 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2011 |
| Externally published | Yes |
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Keywords
- Gastric adenocarcinoma
- High molecular weight kininogen
- MALDI-TOF MS
- Proteomics
- Serum biomarkers
ASJC Scopus subject areas
- Gastroenterology
Cite this
Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis. / Umemura, Hiroshi; Togawa, Akira; Sogawa, Kazuyuki; Satoh, Mamoru; Mogushi, Kaoru; Nishimura, Motoi; Matsushita, Kazuyuki; Tanaka, Hiroshi; Takizawa, Hirotaka; Kodera, Yoshio; Nomura, Fumio.
In: Journal of Gastroenterology, Vol. 46, No. 5, 05.2011, p. 577-585.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis
AU - Umemura, Hiroshi
AU - Togawa, Akira
AU - Sogawa, Kazuyuki
AU - Satoh, Mamoru
AU - Mogushi, Kaoru
AU - Nishimura, Motoi
AU - Matsushita, Kazuyuki
AU - Tanaka, Hiroshi
AU - Takizawa, Hirotaka
AU - Kodera, Yoshio
AU - Nomura, Fumio
PY - 2011/5
Y1 - 2011/5
N2 - Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.
AB - Background: Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific. Methods: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66). Results: Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients. Conclusions: Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.
KW - Gastric adenocarcinoma
KW - High molecular weight kininogen
KW - MALDI-TOF MS
KW - Proteomics
KW - Serum biomarkers
UR - http://www.scopus.com/inward/record.url?scp=79958766040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958766040&partnerID=8YFLogxK
U2 - 10.1007/s00535-010-0369-3
DO - 10.1007/s00535-010-0369-3
M3 - Article
C2 - 21298293
AN - SCOPUS:79958766040
VL - 46
SP - 577
EP - 585
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 5
ER -